Journal
ANNALS OF INTERNAL MEDICINE
Volume 138, Issue 7, Pages 560-570Publisher
AMER COLL PHYSICIANS
DOI: 10.7326/0003-4819-138-7-200304010-00012
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA92594] Funding Source: Medline
- NIDDK NIH HHS [DK56645] Funding Source: Medline
Ask authors/readers for more resources
Basic studies of DNA replication and repair have provided surprising and pivotal insights into a novel pathway of tumorigenesis. Defects in the DNA mismatch repair process dramatically increase the risk for specific types of cancer because of instability in microsatellite DNA sequences. A germline mutation in either the hMSH2 or hMLH1 mismatch repair gene results in the hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch, syndrome. The lifetime risk for colon cancer is 80% in affected persons, and an aggressive cancer surveillance program is essential not only for these individuals but also for at-risk family members. The diagnosis of HNPCC can be made by fulfillment of the Amsterdam clinical criteria or through genetic testing for germline mutations in hMSH2 or hMLH1. Genetic testing is particularly useful in families with atypical clinical features and also for cancer risk assessment within an established HNPCC kindred. Microsatellite instability (MSI) of DNA is a hallmark feature of HNPCC-associated tumors, and as many as 15% of cases of sporadic colorectal cancer also display MSI. The biological behavior of colorectal tumors with MSI is distinctive; the most intriguing feature is their favorable natural history. The study of HNPCC has provided an example of the powerful interplay between molecular genetics and clinical care.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available